FDA Approves Capecitabine Plus Docetaxel for Metastatic Breast Cancer

The US Food and Drug Administration (FDA)
recently approved the use of capecitabine (Xeloda) in combination with docetaxel
(Taxotere) for the treatment of metastatic breast cancer in patients who failed
anthracycline therapy. This regimen is the first chemotherapy combination to
significantly extend survival (by 3 months) in these patients compared to
docetaxel alone.

Previously, docetaxel monotherapy (100 mg/m² on day 1 of each
21-day cycle) was the only regimen to demonstrate improved survival over that
achieved with the standard combination regimen of mitomycin (Mutamycin) and
vinblastine. Recent findings indicate that patients treated with the combination
of capecitabine and docetaxel had a superior survival and a 22.5% reduced risk
of mortality (hazard ratio: 0.775, P = .013) compared to those treated with
docetaxel alone. In addition, the combination produced significantly superior
tumor response rates (32% vs 22% for docetaxel alone) and longer time to disease
progression (6.1 months vs 4.2 months).

"Xeloda combined with Taxotere is an important treatment
improvement for women with metastatic breast cancer," said Joyce O’Shaughnessy,
md, codirector of breast cancer research at Baylor-Sammons Cancer Center and US
Oncology. "The clinical data showed significant improvements in survival,
tumor response, and time to disease progression for the combination compared to
Taxotere alone in patients after failure of anthracycline treatment. This
represents a major advance in the management of women with metastatic breast
cancer, as improvements in survival are the bottom line."

Clinical Trial Results

The FDA decision was based on the results of a large phase III
trial in 511 patients that compared capecitabine in combination with docetaxel
to docetaxel alone and looked at survival, time to disease progression, and
tumor response rate. Women with metastatic breast cancer who had failed
treatment with an anthracycline were randomized to either the combination
(oral capecitabine, 1,250 mg/m² twice daily, days 1 to 14 with 1 week of rest,
plus IV docetaxel, 75 mg/m², day 1 of each 21-day treatment cycle) or
monotherapy (IV docetaxel 100 mg/m², day 1 of each 21-day cycle).

The combination produced significantly better outcomes than
docetaxel alone. Median survival among women in the combination group compared
to the monotherapy group was 14.5 vs 11.5 months (P = .013), median time to
disease progression was 6.1 vs 4.2 months (P = .001), and the tumor
response rate was 32% vs 22% (P = .009). The trial was conducted in the United
States, Canada, and Australia, as well as countries in Europe, Asia, and Latin
America.

Adverse events, including diarrhea, stomatitis, hand-foot
syndrome, and nausea and vomiting, were observed more commonly in the
combination therapy group. These effects, however, proved to be manageable with
appropriate medical intervention and dose interruptions. Dose reductions
decreased the overall incidence of these events in subsequent cycles. Patients
who received docetaxel therapy alone experienced a higher incidence of
neutropenic fever, myalgia, and arthralgia.